μ opioid receptor A118G polymorphism in association with striatal opioid neuropeptide in association with striatal opioid neuropeptide gene expression in heroin abusers

Katarina Drakenberg, Andrej Nikoshkov, Monika Cs Horváth, Pernilla Fagergren, Anna Gharibyan, Kati Saarelainen, Sadia Rahman, Ingrid Nylander, Georgy Bakalkin, Jovan Rajs, Eva Keller, Yasmin L. Hurd

Research output: Contribution to journalArticlepeer-review

100 Scopus citations

Abstract

μ Opioid receptors are critical for heroin dependence, and A118G SNP of the μ opioid receptor gene (OPRM1) has been linked with heroin abuse. In our population of European Caucasians (n = 118), ≈90% of 118G allelic carriers were heroin users. Postmortem brain analyses showed the OPRM1 genotype associated with transcription, translation, and processing of the human striatal opioid neuropeptide system. Whereas down-regulation of preproenkephalin and preprodynorphin genes was evident in all heroin users, the effects were exaggerated in 118G subjects and were most prominent for preproenkephalin in the nucleus accumbens shell. Reduced opioid neuropeptide transcription was accompanied by increased dynorphin and enkephalin peptide concentrations exclusively in 118G heroin subjects, suggesting that the peptide processing is associated with the OPRM1 genotype. Abnormal gene expression related to peptide convertase and ubiquitin/proteosome regulation was also evident in heroin users. Taken together, alterations in opioid neuropeptide systems might underlie enhanced opiate abuse vulnerability apparent in 118G individuals.

Original languageEnglish
Pages (from-to)7883-7888
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume103
Issue number20
DOIs
StatePublished - 16 May 2006
Externally publishedYes

Keywords

  • Drug abuse
  • Dynorphin
  • Enkephalin
  • mRNA

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